Simple Self-Assembled Targeting DNA Nano Sea Urchin as a Multivalent Drug Carrier

Abstract

An ideal drug delivery platform with high cell selectivity, drug payload capacity, and cellular internalization capability is usually of the essence for targeted cancer chemotherapy. Herein, by combining palindromic DNA strands with a targeting aptamer probe, we demonstrated a self-assembled nanoscale sea urchin-shaped structure (called aptamer-NSU) as a multivalent carrier capable of executing targeted cancer cell imaging and drug delivery. The DNA nanostructure is composed of a spherical trunk and surface-confined spines: the former is assembled from only one biotinylated DNA containing four different palindrome domains, and the latter is a biotinylated aptamer (Sgc8) conjugated to the trunk surface via streptavidin−biotin affinity interaction. The spherical trunk can densely load doxorubicin (Dox), and the surface-confined Sgc8 probes can function as targeting moieties to specifically bind to target cells in a polyvalent-binding fashion. Atomic force microscopy (AFM) and gel electrophoresis show the assembly of Sgc8-NSU. The confocal fluorescence imaging demonstrates that fluorescently labeled Sgc8-NSU can specifically image CEM cells. Flow cytometric analyses indicate that Sgc8-NSU exhibits the multivalent binding effect, achieving the significant improvement in binding affinity and selectivity compared with free Sgc8. Moreover, the CCK-8 assay confirmed that Dox-loaded Sgc8-NSU induces an enhanced cellular cytotoxicity to target cancer cells but not to negative nontarget cells. The developed DNA nanoplatform is expected to provide a valuable insight into constructing structural DNA nanotechnology-based drug delivery nanovehicles suitable for targeted cancer therapy.

Direct visualization of superselective colloid-surface binding mediated by multivalent interactions

“…This allows for a sharp differentiation of surfaces that consist of the same receptor type but vary in receptor density. Integrating this powerful feature into drug delivery systems would enable highly selective targeting of diseased cells (6)(7)(8): for example, in cancer therapy (9)(10)(11) where tumor cells overexpress receptors on their surface (12,13) or to target viral infections (14).…”

Direct visualization of superselective colloid-surface binding mediated by multivalent interactions

“…[33]. To connect the seemingly different treatments, one only needs to recognise that: exp(−βF ads ) − 1 = q, (10) where the −1 ( as discussed in [43]) stems from the fact that we consider as bound only colloids where at least a single bond is present, whereas F ads is calculated using the zero-energy reference as a state with no bonds. Substituting our experimental parameters in Eq.…”

“…for example, in cancer therapy [9][10][11] where tumor cells over-express receptors on their surface [12,13], or to target viral infections [14].…”

Multivalent Aptamer Approach: Designs, Strategies, and Applications

“…For spherical multivalent aptamers, the aptamers are connected onto a hollow or solid core particle in an organized and radial polyvalent arrangement [ 31 ]. The core particles can be gold [ 32 ], silver [ 33 ], metal oxides [ 34 , 35 , 36 ], silica [ 37 , 38 ], polymers [ 39 ], or DNA self-assemblies [ 40 ]. Spherical carriers allow the greatest directional extension of aptamers into sample solutions, resulting in enhanced contact surface areas and thus better aptamer–target interactions.…”